My long term objectives are to clarify the biologic relevance of toxin-induced, acute changes in phase II-conjugation/detoxication enzymes, particularly the glutathione S-transferases (GSH S-t). Specific aims of this application concern the rapid decrease in liver cytosol GSH S-t which I have recently observed in fasted animals given the model hepatotoxin 1,1-dichloroethylene (1,1-DCE). Time-course studies with I4C-1,1-DCE will determine if the decrease in GSH S-t activities precedes (1) decreased biliary excretion of detoxified GSH conjugates of the toxin, and 2) injurious covalent binding of reactive intermediates of the toxin to cell constituents. GSH S-t isozyme will be separated, and examined for changes in apparent Vmax and Km, and for covalent binding of 1,1-DCE metabolites. 14 C-lysine will be given to determine if 1,1-DCE induces rapid synthesis of GSH S-t. Possible effects of 1,1-DCE on GSH in microsomes and mitochondria will be evaluated. In addition, I will determine if acetaminophen also rapidly decreases liver GSH S-t activities. This study should clarify the selectivity mechanism and consequences of toxin-induced rapid changes in GSH S-t.